Jean-Philippe Demers

Publications (2)12.69 Total impact

• Source

  Available from: Rodolfo Briones

  Article: beta-Barrel Mobility Underlies Closure of the Voltage-Dependent Anion Channel

  Ulrich Zachariae, Robert Schneider, Rodolfo Briones, Zrinka Gattin, Jean-Philippe Demers, Karin Giller, Elke Maier, Markus Zweckstetter, Christian Griesinger, Stefan Becker, Roland Benz, Bert L De Groot, Adam Lange
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  ABSTRACT: The voltage-dependent anion channel (VDAC) is the major protein in the outer mitochondrial mem-brane, where it mediates transport of ATP and ADP. Changes in its permeability, induced by voltage or apoptosis-related proteins, have been implicated in apoptotic pathways. The three-dimensional struc-ture of VDAC has recently been determined as a 19-stranded b-barrel with an in-lying N-terminal helix. However, its gating mechanism is still unclear. Using solid-state NMR spectroscopy, molecular dynamics simulations, and electrophysiology, we show that deletion of the rigid N-terminal helix sharply increases overall motion in VDAC's b-barrel, resulting in elliptic, semicollapsed barrel shapes. These states quantitatively reproduce conductance and selectivity of the closed VDAC conformation. Mutation of the N-terminal helix leads to a phenotype intermediate to the open and closed states. These data suggest that the N-terminal helix controls entry into elliptic b-barrel states which underlie VDAC closure. Our results also indicate that b-barrel chan-nels are intrinsically flexible.
  Structure 07/2012; · 6.35 Impact Factor
• Article: β-Barrel Mobility Underlies Closure of the Voltage-Dependent Anion Channel.

  Ulrich Zachariae, Robert Schneider, Rodolfo Briones, Zrinka Gattin, Jean-Philippe Demers, Karin Giller, Elke Maier, Markus Zweckstetter, Christian Griesinger, Stefan Becker, Roland Benz, Bert L de Groot, Adam Lange
  [show abstract] [hide abstract]
  ABSTRACT: The voltage-dependent anion channel (VDAC) is the major protein in the outer mitochondrial membrane, where it mediates transport of ATP and ADP. Changes in its permeability, induced by voltage or apoptosis-related proteins, have been implicated in apoptotic pathways. The three-dimensional structure of VDAC has recently been determined as a 19-stranded β-barrel with an in-lying N-terminal helix. However, its gating mechanism is still unclear. Using solid-state NMR spectroscopy, molecular dynamics simulations, and electrophysiology, we show that deletion of the rigid N-terminal helix sharply increases overall motion in VDAC's β-barrel, resulting in elliptic, semicollapsed barrel shapes. These states quantitatively reproduce conductance and selectivity of the closed VDAC conformation. Mutation of the N-terminal helix leads to a phenotype intermediate to the open and closed states. These data suggest that the N-terminal helix controls entry into elliptic β-barrel states which underlie VDAC closure. Our results also indicate that β-barrel channels are intrinsically flexible.
  Structure 07/2012; 20(9):1540-9. · 6.35 Impact Factor